OBJECTIVE:To examine the associations between continuous glucose monitoring (CGM) metrics, including glucose management indicator (GMI) and overnight glucose levels, and pregnancy outcomes in women with type 1 diabetes. RESEARCH DESIGN AND METHODS:Secondary exploratory analysis of the CRISTAL trial including 95 pregnant women with type 1 diabetes using CGM. Associations were assessed using logistic regression and Spearman correlations, presented as odds ratios (95% confidence intervals [CIs]) adjusted for baseline HbA1c. GMI validity was assessed using scatter and Bland-Altman plots. RESULTS:Each 5% increase in overall pregnancy-specific time-in-range (TIRp) decreased the odds of gestational hypertension (odds ratio [OR] 0.63, 95% CI 0.41-0.97), birthweight >4.5 kg (OR 0.56, 95% CI 0.32-0.96), and neonatal hypoglycemia requiring hospital care (OR 0.09, 95% CI 0.01-0.57). Each 5% increase in overnight TIRp decreased the odds of gestational hypertension (OR 0.71, 95% CI 0.52-0.98) and neonatal hypoglycemia requiring hospital care (OR 0.15, 95% CI 0.03-0.79). Each 5% increase in overall time-above-range (TARp) increased the odds of birthweight >4.5 kg (OR 1.76, 95% CI 1.05-2.96), respiratory distress (OR 1.55, 95% CI 1.02-2.37), and neonatal hypoglycemia requiring hospital care (OR 5.10, 95% CI 1.14-22.78). Each 5% increase in TARp overnight increased the odds of hospital care for neonatal hypoglycemia (OR 2.55, 95% CI 1.15-5.66). Each 0.28 mmol/L increase in mean glucose and 0.5% increase in GMI were associated with increased respiratory distress (OR 1.54, 95% CI 1.07-2.23 and OR 6.15, 95% CI 1.33-28.40). Every 0.28 mmol/L increase in glycemic variability (SD) was associated with gestational hypertension (OR 1.69, 95% CI 1.02-2.80) and birthweight >4.5 kg (OR 2.31, 95% CI 1.20-4.43). Several combinations of CGM metrics (TIRp[-night], TARp[-night], SD, mean glucose) improved discriminative performance for pregnancy outcomes. GMI and HbA1c values were discordant. CONCLUSIONS:Specific combinations of CGM metrics, including overnight TIRp/TARp, may be informative for predicting pregnancy outcomes. GMI and HbA1c should not be considered interchangeable for glycemic control during pregnancy.

Purpose Women are generally protected against insulin resistance and related comorbidities when compared with men, potentially due to the role of sex hormones. While epidemiological and animal studies suggest that sex hormones may impact insulin sensitivity, studies in humans on the effects of estradiol and testosterone treatment on insulin sensitivity assessed by gold-standard measures remain limited. The molecular mechanisms involved are also not well understood. Therefore, we aimed to investigate changes in insulin sensitivity and associated change in plasma proteome following 3 months of sex hormone therapy. Methods This prospective, observational study included 29 individuals initiating feminizing (estradiol with GnRH analogue; n = 16) or masculinizing (testosterone; n = 13) therapy. Measurements at baseline and after 3 months included insulin sensitivity, assessed via hyperinsulinemic-euglycemic clamp (M-value: adjusted for lean body mass and M/I ratio: M-value adjusted for plasma insulin concentrations), along with plasma proteomics. Results During feminizing hormone therapy, insulin sensitivity increased (M-value: + 23.3%, M/I ratio: + 20.2%; P < .05), whereas during masculinizing hormone therapy, no changes were observed. Of the differentially expressed plasma proteins (49 during feminizing and 356 during masculinizing hormone therapy), 16 correlated with changes in insulin sensitivity. Several were involved in immunoregulation and inflammation (vascular endothelial growth factor D, 5 '-nucleotidase), iron homeostasis and erythropoiesis (hepcidin, transferrin receptor protein 1:cytoplasmic domain), and oxidative stress (superoxide dismutase 3). Conclusion Feminizing hormone therapy, characterized by high serum estradiol and low serum testosterone concentrations, enhanced insulin sensitivity. These findings highlight the impact of sex hormones on insulin sensitivity and may inform sex-specific precision medicine.

OBJECTIVE:The CRISTAL trial indicated that advanced hybrid closed loop (AHCL) therapy with MiniMed™ 780G in type 1 diabetes pregnancy did not improve time in range (TIRp) compared with standard insulin therapy (SoC), but improved TIRp overnight and reduced time below range (TBRp). We aimed to evaluate the effect of AHCL therapy across different subgroups. RESEARCH DESIGN AND METHODS:This secondary analysis of the CRISTAL randomized controlled trial compared glycemic outcomes (TIRp, TIRp overnight, TBRp, and TBRp overnight) averaged over the antenatal period (14-, 20-, 26-, and 33-weeks' gestation) between the AHCL and SoC groups, within subgroups defined by baseline characteristics. RESULTS:In women with baseline HbA1c <7.0%, the AHCL group (n = 35) had a significantly higher TIRp than SoC (n = 37), with a mean difference of 5.64% (95% confidence interval [95% CI]: 1.32-9.96), corresponding to 1 h 21 min more TIRp per day and 11.89% (95% CI: 7.01-16.76) higher TIRp overnight. In women without prior AHCL use, TIRp was 6.29% higher (95% CI: 0.90-11.68) and overnight TIRp 11.91% higher (95% CI: 5.65-18.16) in the AHCL group (n = 24) compared with SoC (n = 28). In women without higher education, AHCL users (n = 14) had a significantly higher TIRp compared with SoC (n = 14) with a difference of 7.33% (95% CI: 0.88-13.78). TBRp was significantly lower in AHCL users with baseline HbA1c <7.0% and in women without prior AHCL use. CONCLUSIONS:AHCL therapy improved glycemic management in pregnant women with baseline HbA1c <7.0%, in women without prior AHCL use, and in women without higher education, indicating that AHCL might particularly benefit these subgroups.

Sex-based disparities in the incidence, prevalence and disease manifestations have been observed across various medical conditions, including type 1 diabetes (T1D). Differences in glycaemic control and quality of life between men and women have been reported, with women experiencing lower rates of glycaemic targets and a higher risk for long-term complications, particularly cardiovascular disease. Additionally, women face a greater economic and mental health burden related to T1D. This narrative review explores the challenges that complicate glycaemic management in women living with T1D, including hormonal influences during puberty, pregnancy and the (peri-) menopausal period. We also summarize current available evidence on the safety and efficacy of the MiniMed™ 780G (MM780G) system in addressing these challenges for women living with T1D. Finally, recent real-world data are reported on the absence of significant sex-related differences in glycaemic outcomes of over 280 000 real-world users of the MM780G, across various age groups from childhood and adolescence to the (peri-) menopausal period.

Aims Continuous glucose monitoring (CGM) is now standard of care for insulin-treated people with diabetes (PwD) and expanding to broader patient groups. Barriers to CGM-related training and awareness among healthcare professionals (HCPs) in different roles should be removed to allow broader access to CGM. We developed a role-based competency framework that stratifies CGM-related knowledge and skills for HCPs interacting with PwD who use CGM. Methods A multidisciplinary, international panel of CGM-experienced clinicians and diabetes educators developed the competence framework. Draft competencies were derived from published guidance, reviewed and refined, then organized into domains and mapped to four responsibility levels. Results The framework comprises four levels (awareness, competence, expertise, leadership) across the domains of system knowledge, clinical application, special situations and leadership. Levels are defined by a HCP’s role rather than professional title. For each level, the framework specifies core knowledge, skills and appropriate referral strategies. The resulting structure helps to reduce implementation barriers and aligns level-specific training with defined clinical responsibilities and tailored referral pathways. Conclusions This consensus-driven, role-oriented framework offers a pragmatic structure for CGM-related education by mapping competencies to different roles and skills, thus enabling HCPs to introduce CGM as a meaningful benefit for both themselves and PwD.

In type 1 diabetes, optimal glucose management during the peripartum period is critical to reduce neonatal hypoglycemia shortly after birth as well as maternal hypoglycemia postpartum when insulin requirements fall quickly. Healthcare professionals and their patients must consider the mode of insulin delivery during the peripartum period, meaning either to keep a person's own subcutaneous insulin delivery mode- including automated insulin delivery (AID) systems - or to switch to an intravenous insulin/glucose infusion. In this article, we review continuation of AID systems during the peripartum period in women with type 1 diabetes. We included data from local and (inter)national guidelines, evidence from recent publications, and combined this with data from our own clinic. We recommend continuing an AID system over switching to manual mode or an insulin/glucose infusion, provided this is preferred by the patient and several basic criteria are fulfilled.

Importance:Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown. Objective:To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants. Design, Setting, and Participants:Randomized, open-label noninferiority trial conducted at 25 Dutch centers from June 2016 to November 2022 with follow-up completed in May 2023. The study enrolled 820 individuals with gestational diabetes and singleton pregnancies between 16 and 34 weeks of gestation who had insufficient glycemic control after 2 weeks of dietary changes (defined as fasting glucose >95 mg/dL [>5.3 mmol/L], 1-hour postprandial glucose >140 mg/dL [>7.8 mmol/L], or 2-hour postprandial glucose >120 mg/dL [>6.7 mmol/L], measured by capillary glucose self-testing). Interventions:Participants were randomly assigned to receive metformin (initiated at a dose of 500 mg once daily and increased every 3 days to 1000 mg twice daily or highest level tolerated; n = 409) or insulin (prescribed according to local practice; n = 411). Glyburide was added to metformin, and then insulin substituted for glyburide, if needed, to achieve glucose targets. Main Outcomes and Measures:The primary outcome was the between-group difference in the percentage of infants born large for gestational age (birth weight >90th percentile based on gestational age and sex). Secondary outcomes included maternal hypoglycemia, cesarean delivery, pregnancy-induced hypertension, preeclampsia, maternal weight gain, preterm delivery, birth injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admission. Results:Among 820 participants, the mean age was 33.2 (SD, 4.7) years). In participants randomized to oral agents, 79% (n = 320) maintained glycemic control without insulin. With oral agents, 23.9% of infants (n = 97) were large for gestational age vs 19.9% (n = 79) with insulin (absolute risk difference, 4.0%; 95% CI, -1.7% to 9.8%; P = .09 for noninferiority), with the confidence interval of the risk difference exceeding the absolute noninferiority margin of 8%. Maternal hypoglycemia was reported in 20.9% with oral glucose-lowering agents and 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, 3.7%-21.2%). All other secondary outcomes did not differ between groups. Conclusions and Relevance:Treatment of gestational diabetes with metformin and additional glyburide, if needed, did not meet criteria for noninferiority compared with insulin with respect to the proportion of infants born large for gestational age. Trial Registration:Netherlands Trial Registry Identifier: NTR6134.

IMPORTANCE Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown. OBJECTIVE To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label noninferiority trial conducted at 25 Dutch centers from June 2016 to November 2022 with follow-up completed in May 2023. The study enrolled 820 individuals with gestational diabetes and singleton pregnancies between 16 and 34 weeks of gestation who had insufficient glycemic control after 2 weeks of dietary changes (defined as fasting glucose >95 mg/dL [>5.3 mmol/L], 1-hour postprandial glucose >140 mg/dL [>7.8 mmol/L], or 2-hour postprandial glucose >120 mg/dL [>6.7 mmol/L], measured by capillary glucose self-testing). INTERVENTIONS Participants were randomly assigned to receive metformin (initiated at a dose of 500 mg once daily and increased every 3 days to 1000 mg twice daily or highest level tolerated; n = 409) or insulin (prescribed according to local practice; n = 411). Glyburide was added to metformin, and then insulin substituted for glyburide, if needed, to achieve glucose targets. MAIN OUTCOMES AND MEASURES The primary outcome was the between-group difference in the percentage of infants born large for gestational age (birth weight >90th percentile based on gestational age and sex). Secondary outcomes included maternal hypoglycemia, cesarean delivery, pregnancy-induced hypertension, preeclampsia, maternal weight gain, preterm delivery, birth injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admission. RESULTS Among 820 participants, the mean age was 33.2 (SD, 4.7) years). In participants randomized to oral agents, 79% (n = 320) maintained glycemic control without insulin. With oral agents, 23.9% of infants (n = 97) were large for gestational age vs 19.9% (n = 79) with insulin (absolute risk difference, 4.0%; 95% CI, -1.7% to 9.8%; P = .09 for noninferiority), with the confidence interval of the risk difference exceeding the absolute noninferiority margin of 8%. Maternal hypoglycemia was reported in 20.9% with oral glucose-lowering agents and 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, 3.7%-21.2%). All other secondary outcomes did not differ between groups. CONCLUSIONS AND RELEVANCE Treatment of gestational diabetes with metformin and additional glyburide, if needed, did not meet criteria for noninferiority compared with insulin with respect to the proportion of infants born large for gestational age.

Diabetes is among the most prevalent chronic diseases worldwide, with incidence rising each year, shaped by social inequities which influence both vulnerability to disease and access to quality care. These inequities and their systemic drivers are collectively termed the Social Determinants of Health (SDOH). Pregnancy introduces additional physiological and social challenges that can intensify existing inequities. For individuals with diabetes, pregnancy can compound adverse SDOH, increasing both risks and disparities in perinatal outcomes. To effectively manage pregestational diabetes, healthcare professionals must expand their clinical knowledge to understand impact of SDOH, and systematically screen and refer to relevant social support programs. The root causes of SDOH lie in the systems and policies; engaging in advocacy is only way to enact systemic change and complements any individual-level efforts. This review aims to improve adverse perinatal outcomes by providing practical clinical tools to address SDOH in pregestational diabetes in European context.

People with type 1 or type 2 diabetes mellitus (T1DM or T2DM) often experience cognitive impairment. We profiled cells in the nucleus basalis of Meynert (NBM) in postmortem human brain tissue to investigate the neuropathological changes. Sixty-eight postmortem NBM samples were grouped as T1DM, T2DM, and controls without diabetes, with Braak stage 0–II or III–VI. T1DM subjects had only Braak stage 0–II and were thus compared only to controls with a similar Braak stage and not subjects with Braak stage III–VI. We analyzed neurons expressing choline acetyltransferase (ChAT), phosphorylated tau, amyloid-beta, glial cells, and vasculature with their respective markers. We found significantly lower neuronal expression of ChAT in T1DM individuals than in controls and T2DM individuals with Braak stage 0–II. Later-stage hyperphosphorylated tau levels were higher in T2DM compared to controls with Braak stage III–VI. Our results suggest that reduced acetylcholine production by NBM neurons may underlie the cognitive complaints of people with T1DM. In contrast, T2DM may exacerbate neuropathological changes associated with Alzheimer’s disease-like alterations.

Women with type 1 diabetes experience changes in insulin requirements in pregnancy and throughout the menstrual cycle. It remains to be explored whether women with type 1 diabetes perceive changes in glucose regulation during and after the menopausal transition, another period of marked hormonal change in a woman’s life. We conducted a cross-sectional survey to investigate whether women with type 1 diabetes perceive changes in glucose regulation after their final menstrual period. The online questionnaires were distributed through advertisements in hospitals and through online platforms for people living with type 1 diabetes in the Netherlands. Postmenopausal women (≥1 year of amenorrhoea) with type 1 diabetes, aged 45–65 years, were included. Participants with primary amenorrhoea, premenopausal hysterectomy or a postmenopausal diabetes diagnosis were excluded from the study. The primary outcome was the extent to which participants perceived changes in their glucose regulation following their final menstrual period, assessed using a five-point Likert scale. Menopausal symptom severity was estimated using the Greene climacteric scale (GCS). Questionnaires from a total of 159 women were eligible for inclusion. Participants had a mean age of 54.9 years (SD 3.8), a mean diabetes duration of 30.3 years (SD 12.8), and had their final menstrual period at a mean age of 50.1 years (SD 5.0). Overall, 67.4 https://doi.org/10.34894/84QJOO .

Background A multicentre, randomised controlled trial (the CRISTAL trial), demonstrated the safety and efficacy of MiniMedTM 780G advanced hybrid closed loop (AHCL) therapy during pregnancy, showing improved glycaemic control overnight, less hypoglycaemia, and improved treatment satisfaction compared to standard insulin therapy (SoC, mainly open-loop insulin pump therapy). This study aimed to assess the cost-effectiveness of AHCL, which has a higher initial cost, compared to SoC in pregnant women with type 1 diabetes (T1D). Methods A decision tree model was developed to estimate the cost-effectiveness of AHCL compared to SoC in pregnant women with T1D, covering pregnancy to birth and postpartum hospital discharge (a time horizon of 28 weeks). Total costs per strategy (in 2024 euros, ) were calculated from a healthcare payer perspective. The base- case analysis derived prevalence of pregnancy complications and hospitalisations directly related to diabetes management from the CRISTAL trial. Uncertainty was analysed by exploring multiple scenarios and sensitivity analyses. Findings In the base-case analysis, the cost of using AHCL during pregnancy was estimated at 13,988.75 (95% CI: 12,240 to 16,062) compared to 14,221.33 (95% CI: 12,380 to 16,420) for SoC, indicating cost-savings of 232.57 per individual, alongside the demonstrated clinical benefits of AHCL. The primary cost driver was the AHCL device cost. This cost was offset by savings from shorter and less frequent hospital admissions (mainly due to severe hypoglycaemia and dysregulated diabetes) in the AHCL group compared to SoC. In our probabilistic sensitivity analysis, AHCL was dominant in 73% of the simulated cost-effectiveness pairs. Interpretation AHCL might be cost-saving compared to SoC for pregnant women with T1D. However, more robust data are needed to assess the potential impact of AHCL therapy on pregnancy and long-term health outcomes. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The use of GLP1-agonists and SGLT2 inhibitors among inpatients increases due to their favorable metabolic, cardiovascular, and renal effects. However, there are concerns regarding their perioperative safety, because of delayed gastric emptying associated with GLP1-agonists which potentially increases aspiration risk, and the risk of (euglycemic) ketoacidosis associated with the use of SGLT2 inhibitors. To avoid these potential complications, it is currently advised to stop GLP1-agonists one dose preoperatively and SGLT2 inhibitors for three days, both of which carries a risk for glucose dysregulation. Since the effect of GLP1-agonists on gastric emptying diminishes with long-term use, we argue that GLP1-agonists can be continued. Also, we argue that SGLT2 inhibitors can be safely continued provided that glucose and insulin are administered perioperatively in patients with type 2 diabetes mellitus, with blood gas measurements among those without type 2 diabetes with an increased risk of ketoacidosis.